tbuckley/cabot-search huggingface dataset:
Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration
Authors: Beatrice Paola Festa, Farah H. Siddiqi, Maria Jimenez-Sanchez, Hyeran Won, Matea Rob, Alvin Djajadikerta, Eleanna Stamatakou, David C. Rubinsztein
Journal: Neuron (2023)

In neurodegenerative diseases, microglia switch to an activated state, which results in excessive secretion of pro-inflammatory factors. Our work aims to investigate how this paracrine signaling affects neuronal function. Here, we show that activated microglia mediate non-cell-autonomous inhibition of neuronal autophagy, a degradative pathway critical for the removal of toxic, aggregate-prone proteins accumulating in neurodegenerative diseases. We found that the microglial-derived CCL-3/-4/-5 bind and activate neuronal CCR5, which in turn promotes mTORC1 activation and disrupts autophagy and aggregate-prone protein clearance. CCR5 and its cognate chemokines are upregulated in the brains of pre-manifesting mouse models for Huntington's disease (HD) and tauopathy, suggesting a pathological role of this microglia-neuronal axis in the early phases of these diseases. CCR5 upregulation is self-sustaining, as CCL5-CCR5 autophagy inhibition impairs CCR5 degradation itself. Finally, pharmacological or genetic inhibition of CCR5 rescues mTORC1 hyperactivation and autophagy dysfunction, which ameliorates HD and tau pathologies in mouse models.
Pyrrolopyrrole aza-BODIPY-based NIR-II fluorophores for in vivo dynamic vascular dysfunction visualization of vascular-targeted photodynamic therapy
Authors: Shuaishuai Bian, Xiuli Zheng, Weimin Liu, Jihao Li, Zekun Gao, Haohui Ren, Wenjun Zhang, Chun-Sing Lee, Pengfei Wang
Journal: Biomaterials (2023)
Reversal of hepatic fibrosis by the co-delivery of drug and ribonucleoprotein-based genome editor
Authors: Jiayu Gu, Jingfang Sun, Kun Tian, Jinlei Bian, Juanjuan Peng, Shu Xu, Lingzhi Zhao
Journal: Biomaterials (2023)

Liver fibrosis is a chronic disease without effective treatment in the clinic. Gene editing systems such as the well-known CRISPR/Cas9 have shown great potential in the biomedical field. However, the delivery of the ribonucleoprotein is challenging due to the unstable RNA probe and the requirement for the entrance to the nucleus. Recently, a structure-guided endonuclease (SGN) has been reported as an effective gene-editing system composed of a nuclease and stable DNA probes, which can regulate the protein expression by targeting specific mRNA outside the nucleus. Here, we conjugated the SGN to a nanomicelle as the delivery system. In the resulting material, the chance of the collision between the endonuclease and the probe was raised due to the confinement of the two components within the 40-nm nanomicelle, thus the mRNA can be cleaved immediately after being captured by the probe, resulting in a space-induced nucleotide identification-cleavage acceleration effect. The delivery system was used to treat liver fibrosis via the co-delivery of SGN and a drug rosiglitazone to the hepatic stellate cells, which separately downregulated the expression of tissue inhibitor of metalloprotease-1 and inactivated the hepatic stellate cells. The system successfully reversed the liver fibrosis in mice through the bidirectional regulatory that simultaneously promoted the degradation and inhibited the production of the collagen, demonstrating the great potency of the SGN system as gene medicine.
Endoscopic ultrasound-guided fine-needle aspiration of periarterial tumor extension from mucinous cystic carcinoma
Authors: Shinichi Takano, Mitsuharu Fukasawa, Naruki Shimamura, Shota Harai, Yoshimitsu Fukasawa, Satoshi Kawakami, Nobuyuki Enomoto
Journal: Endoscopy (2023)

A 57-year-old woman with abdominal pain was admitted to our hospital for close examination. The imaging studies revealed a cystic tumor in the pancreatic tail. The cystic mass, 6 cm in size, was accompanied by internal mural nodules ([Fig. 1 a]), and periarterial tumor extension from the splenic artery to the celiac and common hepatic arteries with encasement ([Fig. 1 b, c]). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of cystic tumors is a safe technique [1]. However, there are still some concerns about peritoneal dissemination after EUS-FNA of cystic masses [2]. In this context, we decided to perform EUS-FNA of the periarterial tumor extension around the splenic artery ([Fig. 2 a], [Video 1]) instead of puncturing the cystic mass.
Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study
Authors: Aita Signorell, Phyllis Awor, Jean Okitawutshu, Antoinette Tshefu, Elizabeth Omoluabi, Manuel W. Hetzel, Proscovia Athieno, Joseph Kimera, Gloria Tumukunde, Irene Angiro, Jean-Claude Kalenga, Babatunde K. Akano, Kazeem Ayodeji, Charles Okon, Ocheche Yusuf, Giulia Delvento, Tristan T. Lee, Nina C. Brunner, Mark J. Lambiris, James Okuma, Nadja Cereghetti, Valentina Buj, Theodoor Visser, Harriet G. Napier, Christian Lengeler, Christian Burri
Journal: PLoS Medicine (2023)

[This corrects the article DOI: 10.1371/journal.pmed.1004189.].
Endoscopic removal of a large ingested squeeze ball at the duodenojejunal flexure using multiple devices
Authors: Yoshimasa Kubota, Tesshin Ban, Takuya Takahama, Shun Sasoh, Tsuyoshi Itoh, Yoshinori Nakamura, Takashi Joh
Journal: Endoscopy (2023)

Clinical guidelines recommend endoscopic removal using a basket catheter for blunt and spherical foreign bodies in the small bowel; however, objects with a diameter more than 2.0–2.5 cm cannot typically be passed through the pylorus [1]. This article describes the endoscopic removal of a large ingested squeeze ball at the duodenojejunal flexure using multiple devices.
A novel strategy facilitating endoscopic submucosal dissection of proximal colonic lesions: the rubber band and sheath method
Authors: Hirofumi Abe, Takashi Toyonaga, Douglas Motomura, Ryosuke Ishida, Hiroya Sakaguchi, Tetsuya Yoshizaki, Yuzo Kodama
Journal: Endoscopy (2023)

A 70-year-old woman was referred to our hospital for the treatment of a laterally spreading tumor in the ascending colon ([Fig. 1]). Endoscopic submucosal dissection (ESD) was performed using a novel strategy with an orthodontic elastic rubber band (Latex Elastics Light 8 mm; Tomy International, Osaka, Japan) and EndoTrac (EndoTrac T type; Top, Tokyo, Japan) ([Fig. 2], [Video 1]) [1]. The latter is a traction device composed of a plastic sheath and a line with an adjustable loop at its tip.
Over-the-wire technique in ERCP for common bile duct stone after total gastrectomy with jejunal interposition
Authors: Yuki Ikeda, Toshinori Okuda, Norito Suzuki, Ginji Oomori, Shota Yamada, Shinya Minami
Journal: Endoscopy (2023)

The main reconstruction procedure presently used after total gastrectomy is the Roux-en-Y method, but jejunal interposition was previously performed [1]. The most appropriate technique for endoscopic retrograde cholangiopancreatography (ERCP) after jejunal interposition has not been determined because of a lack of reported cases.
Response to Comment on Duarte et al. Systematic Review and Network Meta-analysis of Neurostimulation for Painful Diabetic Neuropathy. Diabetes Care 2022;45:2466–2475
Authors: Rui V. Duarte, Sarah Nevitt, Sue Copley, Michelle Maden, Cecile C. de Vos, Rod S. Taylor, Sam Eldabe
Journal: Diabetes Care (2023)

Sharan et al. (1) and Sadeghirad et al.(2) raise important points regarding the data sets used in our article (3) and whether a network meta-analysis (NMA) is appropriate.We appreciate the opportunity to respond.We agree that it would have been preferable for our NMA to follow an intention-to-treat (ITT) approach.Although we are aware of the publicly available ITT analysis for the study of highfrequency spinal cord stimulation (SCS), ITT analysis was only available for 50% pain reduction at the 3-month follow-up.Comparable outcome data were not available for the studies of low-frequency SCS at the 3-month follow-up.Therefore, we were unable to compare the studies based on an ITT approach for any outcome.The results and conclusion are based on the available data.No long-term data are available that are appropriate to inform comparisons in the NMA, since crossover was allowed at 6-month follow-up in the included trials.Furthermore, Sadeghirad et al.(2) highlight the results of another subgroup analysis.The results of the primary comparison of SCS to placebo/sham showed significant improvements in pain (pooled mean difference À1.15 [95% CI À1.75 to À0.55, P = 0.001]) (4).This review,
Comment on Tang et al. The Impact of Carbamylation and Anemia on HbA1c’s Association With Renal Outcomes in Patients With Diabetes and Chronic Kidney Disease. Diabetes Care 2023;46:130–137
Authors: Ninon Foussard, Alice Larroumet, Amandine Ferrière, Laurence Blanco, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2023)
Endoscopic cyanoacrylate injection with gel immersion method improved the visual field in profuse gastric variceal hemorrhage
Authors: Daisuke Orita, Tsukasa Ishida, Yoshihiro Okabe, Yuichi Hirata, Michitaka Kohashi, Takuya Mimura, Akihiko Nishizawa
Journal: Endoscopy (2023)

Endoscopic cyanoacrylate injection is recommended for gastric variceal hemorrhage (GVH) as a means of achieving urgent endoscopic hemostasis [1] [2]. However, it can sometimes be technically difficult to secure the visual field because GVH produces a large amount of blood and bloody clots immediately fill the fundus. Gel immersion endoscopy (GIE) is useful for identification of the gastrointestinal bleeding point as it offers a secure visual field [3] [4] [5]. We report a case of successful hemostasis for GVH using cyanoacrylate injection under GIE ([Video 1]).
Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a <i>TREM2</i> -dependent manner in mice
Authors: Samira Parhizkar, Grace Gent, Yun Chen, Nicholas Rensing, Maud Gratuze, Gregory Strout, Sanja Sviben, Eric Tycksen, Qiang Zhang, Petra Erdmann Gilmore, Robert Sprung, Jim Malone, Wei Chen, Javier Remolina Serrano, Xin Bao, Choonghee Lee, Chanung Wang, Eric Landsness, James Fitzpatrick, Michael Wong, Reid Townsend, Marco Colonna, Robert E. Schmidt, David M. Holtzman
Journal: Science Translational Medicine (2023)

Sleep loss is associated with cognitive decline in the aging population and is a risk factor for Alzheimer’s disease (AD). Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-β (Aβ) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice. We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression. Sleep deprivation not only enhanced TREM2-dependent Aβ plaque deposition compared with 5xFAD mice with normal sleeping patterns but also induced microglial reactivity that was independent of the presence of parenchymal Aβ plaques. We investigated lysosomal morphology using transmission electron microscopy and found abnormalities particularly in mice without Aβ plaques and also observed lysosomal maturation impairments in a TREM2-dependent manner in both microglia and neurons, suggesting that changes in sleep modified neuro-immune cross-talk. Unbiased transcriptome and proteome profiling provided mechanistic insights into functional pathways triggered by sleep deprivation that were unique to TREM2 and Aβ pathology and that converged on metabolic dyshomeostasis. Our findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further Aβ deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.
Metformin and Cancer: Solutions to a Real-World Evidence Failure
Authors: Oriana Hoi Yun Yu, Samy Suissa
Journal: Diabetes Care (2023)

The quest to repurpose metformin, an antidiabetes drug, as an agent for cancer prevention and treatment, which began in 2005 with an observational study that reported a reduction in cancer incidence among metformin users, generated extensive experimental, observational, and clinical research. Experimental studies revealed that metformin has anticancer effects via various pathways, potentially inhibiting cancer cell proliferation. Concurrently, multiple nonrandomized observational studies reported remarkable reductions in cancer incidence and outcomes with metformin use. However, these studies were shown, in 2012, to be affected by time-related biases, such as immortal time bias, which tend to greatly exaggerate the benefit of a drug. The observational studies that avoided these biases did not find an association. Subsequently, the randomized trials of metformin for the treatment of type 2 diabetes and as adjuvant therapy for the treatment of various cancers, advanced or metastatic, did not find reductions in cancer incidence or outcomes. Most recently, the largest phase 3 randomized trial of metformin as adjuvant therapy for breast cancer, which enrolled 3,649 women with a 5-year follow-up, found no benefit for disease-free survival or overall survival with metformin. This major failure of observational real-world evidence studies in correctly assessing the effects of metformin on cancer incidence and outcomes was caused by preventable biases which, surprisingly, are still prominent in 2022. Rigorous approaches for observational studies that emulate randomized trials, such as the incident and prevalent new-user designs along with propensity scores, avoid these biases and can provide more accurate real-world evidence for the repurposing of drugs such as metformin.
Endoscopic submucosal dissection of rectal lesion recurrence at the anastomosis site: when the staples lead the way
Authors: Ana Rita Franco, André Mascarenhas, Raquel R. Mendes, Catarina O’Neill, Bruno Pereira, Pedro Barreiro, Cristina Chagas
Journal: Endoscopy (2023)

A 75-year-old man underwent an anterior rectum resection due to an early neoplastic rectal lesion. On surveillance endoscopy 4 years later, the surgical anastomosis was identified at 8 cm from the anal margin and was associated with a 35-mm lateral spreading tumor (LST), compatible with neoplastic recurrence. The LST reached the anastomosis as well as an adjacent pseudodiverticular recess ([Fig. 1]). White-light and narrow-band imaging evaluation looking for signs of invasive disease were unremarkable, so endoscopic submucosal dissection (ESD) was decided upon.
Novel sheath-assisted endoscopic ultrasound-guided drainage for pericholecystic abscess
Authors: Koichiro Mandai, Yukari Kanemitsu, Shiho Nakamura
Journal: Endoscopy (2023)

Recently, a newly designed endoscopic sheath (outer diameter, 8.5 Fr; inner diameter, 6 Fr; UMIDAS sheath cannula; UMIDAS Inc, Kanagawa, Japan) has become available in Japan ([Fig. 1]). Here, we describe a novel sheath-assisted endoscopic ultrasound (EUS)-guided drainage procedure for a pericholecystic abscess.
Epidemiology, biology, and management of venous thromboembolism in gliomas: An interdisciplinary review
Authors: Jasmin Jo, Maria Diaz, Craig Horbinski, Nigel Mackman, Stephen Bagley, Marika Broekman, Janusz Rak, James Perry, Ingrid Pabinger, Nigel S Key, David Schiff
Journal: Neuro-Oncology (2023)

Abstract Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.
Successful treatment of a colonic cyst by endoscopic aspiration and sclerotherapy
Authors: Zhang Tao, Jie Liu, Dan Hu, Ya Lan Chen, Feng Li, Feng Ying Lin, Shenggang Feng
Journal: Endoscopy (2023)

A 38-year-old man presented to our department with constipation that had persisted for 2 years. Upon colonoscopy, we discovered a smooth protrusion (about 2 cm × 2 cm) at the hepatic flexure of his colon ([Fig. 1]). Anechoic ultrasonic colonoscopy was suggestive of a cyst. A transparent puncture needle was used to puncture into the cyst cavity and a syringe was used to aspirate the cyst fluid ([Video 1]). After sufficient aspiration, we verified the disappearance of the cyst ([Fig. 2]) and 2 ml of yellow cyst fluid ([Fig. 3]). Subsequently, 2 ml of polidocanol-methylene blue mixture was injected into the cyst cavity through the puncture needle ([Video 1]). A 6-month follow-up colonoscopy revealed no cyst at the hepatic flexure of the patient's colon ([Fig. 4], [Video 1]).
Factors associated with gallstone disease in the MICOL experience
Authors: A F Attili, R Capocaccia, N Carulli, D Festi, E Roda, L Barbara, L Capocaccia, A Menotti, L Okolicsanyi, G Ricci, L Lalloni, S Mariotti, C Sama, E Scafato
Journal: Hepatology (1997)

The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.
A Placebo-Controlled Trial of Itopride in Functional Dyspepsia
Authors: Gerald Holtmann, Nicholas J. Talley, Tobias Liebregts, Birgit Adam, Christopher Parow
Journal: New England Journal of Medicine (2006)

The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with acetylcholinesterase effects, in patients with functional dyspepsia.
Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy
Authors: Guang-Long Ma, Wei-Feng Lin
Journal: Military Medical Research (2023)

Immune checkpoint blockade (ICB) therapy for cancer has achieved great success both in clinical results and on the market. At the same time, success drives more attention from scientists to improve it. However, only a small portion of patients are responsive to this therapy, and it comes with a unique spectrum of side effects termed immune-related adverse events (irAEs). The use of nanotechnology could improve ICBs' delivery to the tumor, assist them in penetrating deeper into tumor tissues and alleviate their irAEs. Liposomal nanomedicine has been investigated and used for decades, and is well-recognized as the most successful nano-drug delivery system. The successful combination of ICB with liposomal nanomedicine could help improve the efficacy of ICB therapy. In this review, we highlighted recent studies using liposomal nanomedicine (including new emerging exosomes and their inspired nano-vesicles) in associating ICB therapy.
Retraction Note: Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer
Authors: Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
Journal: Molecular Cancer (2023)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-018-0844-7.
The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response
Authors: Alexander Böhner, Manja Jargosch, Nikola S. Müller, Natalie Garzorz-Stark, Caroline Pilz, Felix Lauffer, Rosi Wang, Sophie Roenneberg, Alexander Zink, Jenny Thomas, Fabian J. Theis, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
Journal: Journal of Allergy and Clinical Immunology (2023)
Endoscopic embolization of a refractory bronchobiliary fistula by endoscopic retrograde cholangiography using coils and Histoacryl
Authors: Paul Didden, Rutger C. G. Bruijnen, Evert-Jan P. A. Vonken, Frank P. Vleggaar
Journal: Endoscopy (2023)

Bronchobiliary fistulae are often related to hepatic tumors and also occur after ablative therapy [1] [2]. Endoscopic sphincterotomy or stenting is considered first-line treatment. In case of refractory fistulas, sealing with glue or coils has been suggested, however data are scarce [3] [4].
Endoscopy International Open – recently published
Journal: Endoscopy (2023)

Comment on: Endoscopic vacuum-assisted closure therapy for leakage of the lower gastrointestinal tract: multicenter experiencesEndosc Int Open 2023; 11(02): E212-E217DOI: 10.1055/a-1990-0392 Comment on: Prospective study on the efficacy of endoscopic through-the-scope tack and suture system for gastric peroral endoscopic myotomy mucosal incision site closureEndosc Int Open 2023; 11(02): E187-E192DOI: 10.1055/a-1978-6842 Comment on: EUS-guided left lobe liver biopsy: Safer modality with similar diagnostic yield as right lobe: a pilot studyEndosc Int Open 2023; 11(02): E172-E178DOI: 10.1055/a-1978-6652
Exacerbations in Chronic Obstructive Pulmonary Disease: Clinical, Genetic, and Mycobiome Risk Factors
Authors: Kenki Matsumoto, Nicola Read, Keir E. J. Philip, James P. Allinson
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Exacerbations in Chronic Obstructive Pulmonary Disease: Clinical, Genetic, and Mycobiome Risk Factors." American Journal of Respiratory and Critical Care Medicine, 208(4), pp. 487–489